New therapeutic developments against Shiga toxin-producing Escherichia coli

Microbiology Spectrum

Volumn 2, Issue 5, 2014, Pages

  Melton Celsa, Angela R ^a   O'Brien, Alison D ^a  

^a UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITOXIN; SHIGA TOXIN;

ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); COMPLICATION; DIARRHEA; DRUG DEVELOPMENT; ESCHERICHIA COLI INFECTION; HEMOLYTIC UREMIC SYNDROME; HUMAN; ISOLATION AND PURIFICATION; METABOLISM; MICROBIOLOGY; PATHOLOGY; PRECLINICAL STUDY; SHIGA TOXIN PRODUCING ESCHERICHIA COLI; TRENDS;

ANIMALS; ANTITOXINS; CLINICAL TRIALS AS TOPIC; DIARRHEA; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; ESCHERICHIA COLI INFECTIONS; HEMOLYTIC-UREMIC SYNDROME; HUMANS; SHIGA TOXINS; SHIGA-TOXIGENIC ESCHERICHIA COLI;

EID: 84946096695     PISSN: None     EISSN: 21650497     Source Type: Journal    
DOI: 10.1128/microbiolspec.EHEC-0013-2013     Document Type: Article

References (106)

1. Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, Strasak A, Orth-Holler D, Wurzner R, Karch H. 2012. Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis 54:1413-1421.
2. Palermo MS, Exeni RA, Fernandez GC. 2009. Hemolytic uremic syndrome: pathogenesis and update of interventions. Expert Rev Anti Infect Ther 7:697-707.
3. Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS. 2013. Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 28:2097-2105.
4. Thielman NM, Guerrant RL. 2004. Clinical practice. Acute infectious diarrhea. N Engl J Med 350:38-47.
5. Molbak K, Mead PS, Griffin PM. 2002. Antimicrobial therapy in patients with Escherichia coli O157:H7 infection. JAMA 288:1014-1016.
6. Nelson JM, Griffin PM, Jones TF, Smith KE, Scallan E. 2011. Antimicrobial and antimotility agent use in persons with Shiga toxinproducing Escherichia coli O157 infection in FoodNet sites. Clin Infect Dis 52:1130-1132.
7. Karch H, Goroncy-Bermes P, Opferkuch W, Kroll H-P, O'Brien A. 1985. Subinhibitory concentrations of antibiotics modulate amount of Shiga-like toxin produced by Escherichia coli, p 239-245. In Adam D, Hahn H, Opferkuch W (ed), The Influence of Antibiotics on the Host-Parasite Relationship II. SpringerVerlag, Berlin, Germany.
8. Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. 2000. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342:1930-1936.
9. Slutsker L, Ries AA, Malone K, Wells JG, Greene KD, Griffin PM. 1998. A nationwide case-control study of Escherichia coli O157:H7 infection in the United States. J Infect Dis 177:962-966.
10. Panos GZ, Betsi GI, Falagas ME. 2006. Systematic review: are antibiotics detrimental or beneficial for the treatment of patients with Escherichia coli O157:H7 infection? Aliment Pharmacol Ther 24:731-742.
11. Smith KE, PWilke PR, Reiter PL, Hedican EB, Bender JB, Hedberg CW. 2012. Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic uremic syndrome, Minnesota. Pediatr Infect Dis J 31:37-41.
12. Ikeda K, Ida O, Kimot K, Takatorige T, Nakanishi N, Tatar K. 1999. Effect of early fosfomycin treatment on prevention of hemolytic uremic syndrome accompanying Escherichia coli O157:H7 infection. Clin Nephrol 52:357-362.
13. Fukushima H, Hashizume T, Morita Y, Tanaka J, Azuma K, Mizumoto Y, Kaneno M, Matsuura M, Konma K, Kitani T. 1999. Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996. Pediatr Int 41:213-217.
14. Menne J, Nitschke M, Stingele R, Abu-Tair M, Beneke J, Bramstedt J, Bremer JP, Brunkhorst R, Busch V, Dengler R, Deuschl G, Fellermann K, Fickenscher H, Gerigk C, Goettsche A, Greeve J, Hafer C, Hagenmuller F, Haller H, Herget-Rosenthal S, Hertenstein B, Hofmann C, Lang M, Kielstein JT, Klostermeier UC, Knobloch J, Kuehbacher M, Kunzendorf U, Lehnert H, Manns MP, Menne TF, Meyer TN, Michael C, Munte T, Neumann-Grutzeck C, Nuernberger J, Pavenstaedt H, Ramazan L, Renders L, Repenthin J, Ries W, Rohr A, LRump LC, Samuelsson O, Sayk F, Schmidt BM, Schnatter S, Schocklmann H, Schreiber S, von Seydewitz CU, Steinhoff J, Stracke S, Suerbaum S, van de Loo A, Vischedyk M, Weissenborn K, Wellhoner P, Wiesner M, Zeissig S, Buning J, Schiffer M, Kuehbacher T. 2012. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study. BMJ 345:e4565.
15. Geerdes-Fenge HF, Lobermann M, Nurnberg M, Fritzsche C, Koball S, Henschel J, Hohn R, Schober HC, Mitzner S, Podbielski A, Reisinger EC. 2013. Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-associated diarrhea. Infection 41:669-673.
16. Binks S, Regan K, Richenberg J, Chevassut T. 2012. Microbes without frontiers: severe haemolytic-uraemic syndrome due to E coli O104:H4. BMJ Case Rep 2012.
17. Colic E, Dieperink H, Titlestad K, Tepel M. 2011. Management of an acute outbreak of diarrhoea-associated haemolytic uraemic syndrome with early plasma exchange in adults from southern Denmark: an observational study. Lancet 378:1089-1093.
18. Bielaszewska M, Idelevich EA, Zhang W, Bauwens A, Schaumburg F, Mellmann A, Peters G, Karch H. 2012. Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by epidemic Escherichia coli O104:H4 strain. Antimicrob Agents Chemother 56:3277-3282.
19. Nitschke M, Sayk F, Hartel C, Roseland RT, Hauswaldt S, Steinhoff J, Fellermann K, Derad I, Wellhoner P, Buning J, Tiemer B, Katalinic A, Rupp J, Lehnert H, Solbach W, Knobloch JK. 2012. Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4. JAMA 307:1046-1052.
20. Isogai E, Isogai H, Hayashi S, Kubota T, Kimura K, Fujii N, Ohtani T, Sato K. 2000. Effect of antibiotics, levofloxacin and fosfomycin, on a mouse model with Escherichia coli O157 infection. Microbiol Immunol 44:89-95.
21. Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW. 2000. Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 181: 664-670.
22. Yoshimura K, Fujii J, Taniguchi H, nd S. Yoshida S. 1999. Chemotherapy for enterohemorrhagic Escherichia coli O157:H infection in a mouse model. FEMS Immunol Med Microbiol 26:101-108.
23. Kurioka T, Yunou Y, Harada H, Kita E. 1999. Efficacy of antibiotic therapy for infection with Shiga-like toxin-producing Escherichia coli O157:H7 in mice with protein-calorie malnutrition. Eur J Clin Microbiol Infect Dis 18:561-571.
24. Zangari T, Melton-Celsa AR, Panda A, Boisen N, Smith MA, Taratov I, De Tolla LJ, Nataro JP, O'Brien AD. 2013. Virulence of the Shiga toxin type 2-expressing Escherichia coli O104:H4 German outbreak isolate in two animal models. Infect Immun 81:1562-1574.
25. Al-Qarawi S, Fontaine RE, Al-Qahtani MS. 1995. An outbreak of hemolytic uremic syndrome associated with antibiotic treatment of hospital inpatients for dysentery. Emerg Infect Dis 1:138-140.
26. Scholl D, Cooley M, Williams SR, Gebhart D, Martin D, Bates A, Mandrell R. 2009. An engineered R-type pyocin is a highly specific and sensitive bactericidal agent for the food-borne pathogen Escherichia coli O157:H7. Antimicrob Agents Chemother 53:3074-3080.
27. Ritchie JM, Greenwich JL, Davis BM, Bronson RT, Gebhart D, Williams SR, Martin D, Scholl D, Waldor MK. 2011. An Escherichia coli O157-specific engineered pyocin prevents and ameliorates infection by E. coli O157:H7 in an animal model of diarrheal disease. Antimicrob Agents Chemother 55:5469-5474.
28. Rasko DA, Moreira CG, Li de R, Reading NC, Ritchie JM, Waldor MK, Williams N, Taussig R, Wei S, Roth M, Hughes DT, Huntley JF, Fina MW, Falck JR, Sperandio V. 2008. Targeting QseC signaling and virulence for antibiotic development. Science 321:1078-1080.
29. Crane JK, Byrd IW, Boedeker EC. 2011. Virulence inhibition by zinc in Shiga-toxigenic Escherichia coli. Infect Immun 79:1696-1705.
30. Tesh VL. 2012. The induction of apoptosis by Shiga toxins and ricin. Curr Top Microbiol Immunol 357:137-178.
31. Scheut F, Teel LD, Beutin L, Pierard D, Buvens G, Karch H, Mellmann A, Caprioli A, Tozzoli R, Morabito S, Strockbine NA, Melton-Celsa AR, Sanchez M, Persson S, O'Brien AD. 2012. Multicenter evaluation of a sequence-based protocol for subtyping Shiga toxins and standardizing Stx nomenclature. J Clin Microbiol 50:2951-2963.
32. Bielaszewska M, Friedrich AW, Aldick T, Schurk-Bulgrin R, Karch H. 2006. Shiga toxin activatable by intestinal mucus in Escherichia coli isolated from humans: predictor for a severe clinical outcome. Clin Infect Dis 43:1160-1167.
33. Friedrich AW, Bielaszewska M, Zhang WL, Pulz M, Kuczius T, Ammon A, Karch H. 2002. Escherichia coli harboring Shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis 185:74-84.
34. Lindgren SW, Samuel JE, Schmitt CK, O'Brien AD. 1994. The specific activities of Shiga-like toxin type II (SLT-II) and SLT-II-related toxins of enterohemorrhagic Escherichia coli differ when measured by Vero cell cytotoxicity but not by mouse lethality. Infect Immun 62:623-631.
35. Melton-Celsa AR, Darnell SC, O'Brien AD. 1996. Activation of Shigalike toxins by mouse and human intestinal mucus correlates with virulence of enterohemorrhagic Escherichia coli O91:H21 isolates in orally infected, streptomycin-treated mice. Infect Immun 64:1569-1576.
36. Silberstein C, Copeland DP, Chiang W-L, Repetto HA, Ibarra C. 2008. A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells. J Epithel Biol Pharmacol 1:71-75.
37. Silberstein C, Lucero MS, Zotta E, Copeland DP, Lingyun L, Repetto HA, Ibarra C. 2011. A glucosylceramide synthase inhibitor protects rats against the cytotoxic effects of Shiga toxin 2. Pediatr Res 69:39-394.
38. Armstrong GD, Fodor E, Vanmaele R. 1991. Investigation of Shigalike toxin binding to chemically synthesized oligosaccharide sequences. J Infect Dis 164:1160-1167.
39. Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DW, Weiss R, Kaskel FJ, Spitzer A, Hirschman GH. 2003. Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial. JAMA 290:1337-1344.
40. Takeda T, Yoshino K, Adachi E, Sato Y, Yamagata K. 1999. In vitro assessment of a chemically synthesized Shiga toxin receptor analog attached to chromosorb P (Synsorb Pk) as a specific absorbing agent of Shiga toxin 1 and 2. Microbiol Immunol 43:331-337.
41. Armstrong GD, Rowe PC, Goodyer P, Orrbine E, Klassen TP, Wells G, MacKenzie A, Lior H, Blanchard C, Auclair F, et al. 1995. A phase I study of chemically synthesized verotoxin (Shiga-like toxin) Pktrisaccharide receptors attached to chromosorb for preventing hemolyticuremic syndrome. J Infect Dis 171:1042-1045.
42. Kitov PI, Sadowska JM, Mulvey G, Armstrong GD, Ling H, Pannu NS, Read RJ, Bundle DR. 2000. Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands. Nature 403:66-672.
43. Mulve GL, Marcato P, Kitov PI, Sadowska J, Bundle DR, Armstrong GD. 2003. Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands. J Infect Dis 187:640-649.
44. Nishikawa K, Matsuoka K, Kita E, Okabe N, Mizuguchi M, Hino K, Miyazawa S, Yamasaki C, Aoki J, Takashima S, Yamakawa Y, Nishijima M, Terunuma D, Kuzuhara H, Natori Y. 2002. A therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxinproducing Escherichia coli O157:H7. Proc Natl Acad Sci USA 99:7669-7674.
45. Watanabe M, Matsuoka K, Kita E, Igai K, Higashi N, Miyagawa A, Watanabe T, Yanoshita R, Samejima Y, Terunuma D, Natori Y, Nishikawa K. 2004. Oral therapeutic agents with highly clustered globotriose for treatment of Shiga toxigenic Escherichia coli infections. J Infect Dis 189:360-368.
46. Watanabe-Takahashi M, Sato T, Dohi T, Noguchi N, Kano F, Murata M, Hamabata T, Natori Y, Nishikawa K. 2010. An orally applicable Shiga toxin neutralizer functions in the intestine to inhibit the intracellular transport of the toxin. Infect Immun 78:177-183.
47. Paton AW, Morona R, Paton JC. 2001. Neutralization of Shiga toxins Stx1, Stx2c, and Stx2e by recombinant bacteria expressing mimics of globotriose and globotetraose. Infect Immun 69:1967-1970.
48. Li X, Wu P, Cheng S, Lv X. 2012. Synthesis and assessment of globotriose-chitosan conjugate, a novel inhibitor of Shiga toxins produced by Escherichia coli. J Med Chem 55:2702-2710.
49. Nishikawa K, Watanabe M, Kita E, Igai K, Omata K, Yaffe MB, Natori Y. 2006. A multivalent peptide library approach identifies a novel Shiga toxin inhibitor that induces aberrant cellular transport of the toxin. FASEB J 20:2597-2599.
50. Stearns-Kurosawa DJ, Collins V, Freeman S, Debord D, Nishikawa K, Oh SY, Leibowitz CS, Kurosawa S. 2011. Rescue from lethal Shiga toxin 2-induced renal failure with a cell-permeable peptide. Pediatr Nephrol 26:2031-2039.
51. Tsutsuki K, Watanabe-Takahashi M, Takenaka Y, Kita E, Nishikawa K. 2013. Identification of a peptide-based neutralizer that potently inhibits both Shiga toxins 1 and 2 by targeting specific receptor-binding regions. Infect Immun 81:2133-2138.
52. Paton AW, Morona R, Paton JC. 2000. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat Med 6:265-270.
53. Paton JC, Rogers TJ, Morona R, Paton AW. 2001. Oral administration of formaldehyde-killed recombinant bacteria expressing a mimic of the Shiga toxin receptor protects mice from fatal challenge with Shigatoxigenic Escherichia coli. Infect Immun 69:1389-1393.
54. Pinyon RA, Paton JC, Paton AW, JBotten JA, Morona R. 2004. Refinement of a therapeutic Shiga toxin-binding probiotic for human trials. J Infect Dis 189:1547-1555.
55. Bitzan M, Klemt M, Steffens R, Muller-Wiefel DE. 1993. Differences in verotoxin neutralizing activity of therapeutic immunoglobulins and sera from healthy controls. Infection 21:140-145.
56. Bitzan M, Ludwig K, Klemt M, Konig H, Buren J, Muller-Wiefel DE. 1993. The role of Escherichia coli O157 infections in the classical (enteropathic) haemolytic uraemic syndrome: results of a Central European, multicentre study. Epidemiol Infect 110:183-196.
57. Kimura T, Tani S, Matsumoto Yi Y, Takeda T. 2001. Serum amyloid P component is the Shiga toxin 2-neutralizing factor in human blood. J Biol Chem 276:41576-41579.
58. Kimura T, Tani S, Motoki M, Matsumoto Y. 2003. Role of Shiga toxin 2 (Stx2)-binding protein, human serum amyloid P component (HuSAP), in Shiga toxin-producing Escherichia coli infections: assumption from in vitro and in vivo study using HuSAP and anti-Stx2 humanized monoclonal antibody TMA-15. Biochem Biophys Res Commun 305:1057-1060.
59. Armstrong GD, Mulvey GL, Marcato P, Griener TP, Kahan MC, Tennent GA, Sabin CA, Chart H, Pepys MB. 2006. Human serum amyloid P component protects against Escherichia coli O157:H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome. J Infect Dis 193:1120-1124.
60. Griener TP, Strecker JG, Humphries RM, Mulvey GL, Fuentealba C, Hancock RE, Armstrong GD. 2011. Lipopolysaccharide renders transgenic mice expressing human serum amyloid P component sensitive to Shiga toxin 2. PLoS One 6:e21457.
61. Marcato P, Vander Helm K, Mulvey GL, Armstrong GD. 2003. Serum amyloid P component binding to Shiga toxin 2 requires both a subunit and B pentamer. Infect Immun 71:607-6078.
62. Donohue-Rolfe A, Kondova I, Mukherjee J, Chios K, Hutto D, Tzipori S. 1999. Antibody-based protection of gnotobiotic piglets infected with Escherichia coli O157:H7 against systemic complications associated with Shiga toxin 2. Infect Immun 67:3645-3648.
63. Perera LP, Marques LR, O'Brien AD. 1988. Isolation and characterization of monoclonal antibodies to Shiga-like toxin II of enterohemorrhagic Escherichia coli and use of the monoclonal antibodies in a colony enzyme-linked immunosorbent assay. J Clin Microbiol 26:2127-2131.
64. Strockbine NA, Marques LR, Holmes RK, O'Brien AD. 1985. Characterization of monoclonal antibodies against Shiga-like toxin from Escherichia coli. Infect Immun 50:69-700.
65. Smith MJ, Melton-Celsa AR, Sinclair JF, Carvalho HM, Robinson CM, O'Brien AD. 2009. Monoclonal antibody 11E10, which neutralizes shiga toxin type 2 (Stx2), recognizes three regions on the Stx2 A subunit, blocks the enzymatic action of the toxin in vitro, and alters the overall cellular distribution of the toxin. Infect Immun 77:2730-2740.
66. Smith MJ, Carvalho HM, Melton-Celsa AR, O'Brien AD. 2006. The 13C4 monoclonal antibody that neutralizes Shiga toxin type 1 (Stx1) recognizes three regions on the Stx1 B subunit and prevents Stx1 from binding to its eukaryotic receptor globotriaosylceramide. Infect Immun 74:6992-6998.
67. Sauter KA, Melton-Celsa AR, Larkin K, Troxell ML, O'Brien AD, Magun BE. 2008. Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody. Infect Immun 76:4469-4478.
68. Edwards AC, Melton-Celsa AR, Arbuthnott K, Stinson JR, Schmitt CK, Wong HC, O'Brien AD. 1998. Vero cell neutralization and mouse protective efficacy of humanized monoclonal antibodies against Escherichia coli toxins Stx1 and Stx2, p 388-392. In Kaper JB, O'Brien AD (ed), Escherichia coli O157:H7 and Other Shiga Toxin-Producing E. coli Strains. ASM Press, Washington, DC.
69. Dowling TC, Chavaillaz PA, Young DG, Melton-Celsa A, O'Brien A, Thuning-Roberson C, Edelman R, Tacket CO. 2005. Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal antibody c alpha Stx2 administered intravenously to healthy adult volunteers. Antimicrob Agents Chemother 49:1808-1812.
70. Bitzan M, Poole R, Mehran M, Sicard E, Brockus C, Thuning-Roberson C, Riviere M. 2009. Safety and pharmacokinetics of chimeric anti-Shiga toxin 1 and anti-Shiga toxin 2 monoclonal antibodies in healthy volunteers. Antimicrob Agents Chemother 53:3081-3087.
71. Nakao H, Kataoka C, Kiyokawa N, Fujimoto J, Yamasaki S, Takeda T. 2002. Monoclonal antibody to Shiga toxin 1, which blocks receptor binding and neutralizes cytotoxicity. Microbiol Immunol 46:777-780.
72. Nakao H, Kiyokawa N, Fujimoto J, Yamasaki S, Takeda T. 1999. Monoclonal antibody to Shiga toxin 2 which blocks receptor binding and neutralizes cytotoxicity. Infect Immun 67:5717-5722.
73. Kimura T, Co MS, Vasquez M, Wei S, Xu H, Tani S, Sakai Y, Kawamura T, Matsumoto Y, Nakao H, Takeda T. 2002. Development of humanized monoclonal antibody TMA-15 which neutralizes Shiga toxin 2. Hybrid Hybridomics 21:161-168.
74. Yamagami S, Motoki M, Kimura T, Izumi H, Takeda T, Katsuura Y, Matsumoto Y. 2001. Efficacy of postinfection treatment with anti-Shiga toxin (Stx) 2 humanized monoclonal antibody TMA-15 in mice lethally challenged with Stx-producing Escherichia coli. J Infect Dis 184:738-742.
75. Lopez EL, Contrini MM, Glatstein E, Gonzalez Ayala S, Santoro R, Allende D, Ezcurra G, Teplitz E, Koyama T, Matsumoto Y, Sato H, Sakai K, Hoshide S, Komoriya K, Morita T, Harning R, Brookman S. 2010. Safety and pharmacokinetics of urtoxazumab, a humanized monoclonal antibody, against Shiga-like toxin 2 in healthy adults and in pediatric patients infected with Shiga-like toxin-producing Escherichia coli. Antimicrob Agents Chemother 54:239-243.
76. Mukherjee J, Chios K, Fishwild D, Hudson D, O'Donnell S, Rich SM, Donohue-Rolfe A, Tzipori S. 2002. Production and characterization of protective human antibodies against Shiga toxin 1. Infect Immun 70: 5896-5899.
77. Mukherjee J, Chios K, Fishwild D, Hudson D, O'Donnell S, Rich SM, Donohue-Rolfe A, Tzipori S. 2002. Human Stx2-specific monoclonal antibodies prevent systemic complications of Escherichia coli O157:H7 infection. Infect Immun 70:612-619.
78. Sheoran AS, Chapman S, Singh P, Donohue-Rolfe A, Tzipori S. 2003. Stx2-specific human monoclonal antibodies protect mice against lethal infection with Escherichia coli expressing Stx2 variants. Infect Immun 71:3125-3130.
79. Krautz-Peterson G, Chapman-Bonofiglio S, Boisvert K, Feng H, Herman IM, Tzipori S, Sheoran AS. 2008. Intracellular neutralization of Shiga toxin 2 by an a subunit-specific human monoclonal antibody. Infect Immun 76:1931-1939.
80. Jeong KI, Chapman-Bonofiglio S, Singh P, Lee J, Tzipori S, Sheoran AS. 2010. In vitro and in vivo protective efficacies of antibodies that neutralize the RNA N-glycosidase activity of Shiga toxin 2. BMC Immunol 11:16.
81. Akiyoshi DE, Sheoran AS, Rich CM, Richard L, Chapman-Bonofiglio S, Tzipori S. 2010. Evaluation of Fab and F(ab')2 fragments and isotype variants of a recombinant human monoclonal antibody against Shiga toxin 2. Infect Immun 78:1376-1382.
82. Spooner RA, Watson P, Smith DC, Boal F, Amessou M, Johannes L, Clarkson GJ, Lord JM, Stephens DJ, Roberts LM. 2008. The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network. Biochem J 414:471-484.
83. Guetzoyan LJ, Spooner RA, Boal F, Stephens DJ, Lord JM, Roberts LM, Clarkson GJ. 2010. Fine tuning Exo2, a small molecule inhibitor of secretion and retrograde trafficking pathways in mammalian cells. Mol Biosyst 6:2030-2038.
84. Stechmann B, Bai SK, Gobbo E, Lopez R, Merer G, Pinchard S, Panigai L, Tenza D, Raposo G, Beaumelle B, Sauvaire D, Gillet D, Johannes L, Barbier J. 2010. Inhibition of retrograde transport protects mice from lethal ricin challenge. Cell 141:231-242.
85. Park JG, Kahn JN, Tumer NE, Pang YP. 2012. Chemical structure of Retro-2, a compound that protects cells against ribosome-inactivating proteins. Sci Rep 2:631.
86. Noel R, Gupta N, Pons V, Goudet A, Garcia-Castillo MD, Michau A, Martinez J, Buisson DA, Johannes L, Gillet D, Barbier J, Cintrat JC. 2013. N-methyl dihydroquinazolinones derivatives of Retro-2 with enhanced efficacy against Shiga toxin. J Med Chem 56:3404-3413.
87. Dyve Lingelem AB, Bergan J, Sandvig K. 2012. Inhibitors of intravesicular acidification protect against Shiga toxin in a pH-independent manner. Traffic 13:443-454.
88. Saenz JB, Doggett TA, Haslam DB. 2007. Identification and characterization of small molecules that inhibit intracellular toxin transport. Infect Immun 75:4552-4561.
89. Wahome PG, Bai Y, Neal LM, Robertus JD, Mantis NJ. 2010. Identification of small-molecule inhibitors of ricin and Shiga toxin using a cell-based high-throughput screen. Toxicon 56:313-323.
90. Aletrari MO, McKibbin C, Williams H, Pawar V, Pietroni P, Lord JM, Flitsch SL, Whitehead R, Swanton E, High S, Spooner RA. 2011. Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways. PLoS One 6:e22713.
91. Sekino T, Kiyokawa N, Taguchi T, Ohmi K, Nakajima H, Suzuki T, Furukawa S, Nakao H, Takeda T, Fujimoto J. 2002. Inhibition of Shiga toxin cytotoxicity in human renal cortical epithelial cells by nitrobenzylthioinosine. J Infect Dis 185:785-796.
92. Mukhopadhyay S, Linstedt AD. 2012. Manganese blocks intracellular trafficking of Shiga toxin and protects against Shiga toxicosis. Science 335:332-335.
93. Mukhopadhyay S, Redler B, Linstedt AD. 2013. Shiga toxin-binding site for host cell receptor GPP130 reveals unexpected divergence in toxintrafficking mechanisms. Mol Biol Cell 24:2311-2318.
94. Becker GL, Lu Y, Hardes K, Strehlow B, Levesque C, Lindberg I, Sandvig K, Bakowsky U, Day R, Garten W, Steinmetzer T. 2012. Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases. J Biol Chem 287:21992-22003.
95. Garred O, van Deurs B, Sandvig K. 1995. Furin-induced cleavage and activation of Shiga toxin. J Biol Chem 270:10817-10821.
96. Garred O, Dubinina E, Holm PK, Olsnes S, van Deurs B, Kozlov JV, Sandvig K. 1995. Role of processing and intracellular transport for optimal toxicity of Shiga toxin and toxin mutants. Exp Cell Res 218:39-49.
97. Burgess BJ, Roberts LM. 1993. Proteolytic cleavage at arginine residues within the hydrophilic disulphide loop of the Escherichia coli Shiga-like toxin I A subunit is not essential for cytotoxicity. Mol Microbiol 10:171-179.
98. Stone SM, Thorpe CM, Ahluwalia A, Rogers AB, Obata F, Vozenilek A, Kolling GLKan AV, Magun BE, Jandhyala DM. 2012. Shiga toxin 2-induced intestinal pathology in infant rabbits is A-subunit dependent and responsive to the tyrosine kinase and potential ZAK inhibitor imatinib. Front Cell Infect Microbiol 2:135.
99. Burlaka I, Liu XL, Rebetz J, Arvidsson I, Yang L, Brismar H, Karpman D, Aperia A. 2013. Ouabain protects against Shiga toxin-triggered apoptosis by reversing the imbalance between Bax and Bcl-xL. J Am Soc Nephrol 24:1413-1423.
100. Lapeyraque AL, Malina M, Fremeaux-Bacchi V, Boppel T, Kirschfink M, Oualha M, Proulx F, Clermont MJ, Le Deist F, Niaudet P, Schaefer F. 2011. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 364:2561-2563.
101. Greinache A, Friesecke S, Abel P, Dressel A, Stracke S, Fiene M, Ernst F, Selleng K, Weissenborn K, Schmidt BM, Schiffer M, Felix SB, Lerch MM, Kielstein JT, Mayerle J. 2011. Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial. Lancet 378:1166-1173.
102. Ullrich S, Bremer P, Neumann-Grutzeck C, Otto H, Ruther C, von Seydewitz CU, Meyer GP, Ahmadi-Simab K, Rother J, Hogan B, Schwenk W, Fischbach R, Caselitz J, Puttfarcken J, Huggett S, Tiedeken P, Pober J, Kirkiles-Smith NC, Hagenmuller F. 2013. Symptoms and clinical course of EHEC O104 infection in hospitalized patients: a prospective single center study. PLoS One 8:e55278.
103. Loos S, Ahlenstiel T, Kranz B, Staude H, Pape L, Hartel C, Vester U, Buchtala L, Benz K, Hoppe B, Beringer O, Krause M, Muller D, Pohl M, Lemke J, Hillebrand G, Kreuzer M, Konig J, Wigger M, Konrad M, Haffner D, Oh J, Kemper MJ. 2012. An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. Clin Infect Dis 55:753-759.
104. Hauswaldt S, Nitschke M, Sayk F, Solbach W, Knobloch JK. 2013. Lessons learned from uutbreaks of Shiga toxin producing Escherichia coli. Curr Infect Dis Rep 15:9.
105. Kielstein JT, Beutel G, Fleig S, Steinhoff J, Meyer TN, Hafer C, Kuhlmann U, Bramstedt J, Panzer U, Vischedyk M, Busch V, Ries W, Mitzner S, Mees S, Stracke S, Nurnberger J, Gerke P, WiesnerM, Sucke B, Abu-Tair M, Kribben A, Klause N, Schindler R, Merkel F, Schnatter S, Dorresteijn EM, Samuelsson O, Brunkhorst R. 2012. Best supportive care and therapeutic plasma exchange with or without eculizumab in Shigatoxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant 27:3807-3815.
106. Trachtman H, Austin C, Lewinski M, Stahl RA. 2012. Renal and neurological involvement in typical Shiga toxin-associated HUS. Nat Rev Nephrol 8:658-669.